A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.

Department of Analytical Chemistry Faculty of Natural Sciences Comenius University Ilkovicova 6 842 15 Bratislava Slovakia

Department of Biochemistry Faculty of Medicine Masaryk University Kamenice 5 625 00 Brno Czech Republic

Department of Chemical Drugs Faculty of Pharmacy Masaryk University Palackeho 1946 1 612 00 Brno Czech Republic

Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary Sciences Brno Palackeho tr 1946 1 612 42 Brno Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute Hudcova 296 70 621 00 Brno Czech Republic

Global Change Research Institute CAS Belidla 986 4a 603 00 Brno Czech Republic

Institute of Chemistry University of Silesia in Katowice 40 007 Katowice Poland

Institute of Neuroimmunology Slovak Academy of Sciences Dubravska cesta 9 845 10 Bratislava Slovakia

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacky University Slechtitelu 27 783 71 Olomouc Czech Republic

See more in PubMed

Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet. 2022;399:629–655. doi: 10.1016/S0140-6736(21)02724-0. PubMed DOI PMC

WHO Antimicrobial Resistence. [(accessed on 15 September 2022)]. Available online: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.

Jampilek J. Design and discovery of new antibacterial agents: Advances, perspectives, challenges. Curr. Med. Chem. 2018;25:4972–5006. doi: 10.2174/0929867324666170918122633. PubMed DOI

Jampilek J. Drug repurposing to overcome microbial resistance. Drug Discov. Today. 2022;27:2028–2041. doi: 10.1016/j.drudis.2022.05.006. PubMed DOI

Thomford N.E., Senthebane D.A., Rowe A., Munro D., Seele P., Maroyi A., Dzobo K. Natural products for drug discovery in the 21st century: Innovations for novel drug discovery. Int. J. Mol. Sci. 2018;19:1578. doi: 10.3390/ijms19061578. PubMed DOI PMC

Newman D.J., Cragg G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020;83:770–803. doi: 10.1021/acs.jnatprod.9b01285. PubMed DOI

Atanasov A.G., Zotchev S.B., Dirsch V.M., The International Natural Product Sciences Taskforce. Supuran C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov. 2021;20:200–216. doi: 10.1038/s41573-020-00114-z. PubMed DOI PMC

Saldivar-Gonzalez F.I., Aldas-Bulos V.D., Medina-Franco J.L., Plisson F. Natural product drug discovery in the artificial intelligence era. Chem. Sci. 2022;13:1526–1546. doi: 10.1039/D1SC04471K. PubMed DOI PMC

Hoskins J.A. The occurrence, metabolism and toxicity of cinnamic acid and related compounds. J. Appl. Toxicol. 1984;4:283–292. doi: 10.1002/jat.2550040602. PubMed DOI

Vogt T. Phenylpropanoid biosynthesis. Mol. Plant. 2010;3:2–20. doi: 10.1093/mp/ssp106. PubMed DOI

Shuab R., Lone R., Koul K.K. Cinnamate and cinnamate derivatives in plants. Acta Physiol. Plant. 2016;38:64. doi: 10.1007/s11738-016-2076-z. DOI

Gaikwad N., Nanduri S., Madhavi Y.V. Cinnamamide: An insight into the pharmacological advances and structure-activity relationships. Eur. J. Med. Chem. 2019;181:111561. doi: 10.1016/j.ejmech.2019.07.064. PubMed DOI

Ruwizhi N., Aderibigbe B.A. Cinnamic acid derivatives and their biological efficacy. Int. J. Mol. Sci. 2020;21:5712. doi: 10.3390/ijms21165712. PubMed DOI PMC

Teixeira C., Ventura C., Gomes J.R.B., Gomes P., Martins F. Cinnamic derivatives as antitubercular agents: Characterization by quantitative structure–activity relationship studies. Molecules. 2020;25:456. doi: 10.3390/molecules25030456. PubMed DOI PMC

Sabbah M., Mendes V., Vistal R.G., Dias D.M.G., Zahorszka M., Mikusova K., Kordulakova J., Coyne A.G., Blundell T.L., Abell C. Fragment-based design of Mycobacterium tuberculosis InhA inhibitors. J. Med. Chem. 2020;63:4749–4761. doi: 10.1021/acs.jmedchem.0c00007. PubMed DOI PMC

Alves do Vale J., Rodrigues M.P., Lima A.M.A., Santiago S.S., de Almeida Lima G.D., Andrade Almeida A., Licursi de Oliveira L., Bressan G.C., Teixeira R.R., Machado-Neves M. Synthesis of cinnamic acid ester derivatives with antiproliferative and antimetastatic activities on murine melanoma cells. Biomed. Pharmacother. 2022;148:112689. doi: 10.1016/j.biopha.2022.112689. PubMed DOI

Bunse M., Daniels R., Grundemann C., Heilmann J., Kammerer D.R., Keusgen M., Lindequist U., Melzig M.F., Morlock G.E., Schulz H., et al. Essential oils as multicomponent mixtures and their potential for human health and well-being. Front. Pharmacol. 2022;13:956541. doi: 10.3389/fphar.2022.956541. PubMed DOI PMC

Gonec T., Zadrazilova I., Nevin E., Kauerova T., Pesko M., Kos J., Oravec M., Kollar P., Coffey A., O’Mahony J., et al. Synthesis and biological evaluation of N-alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides. Molecules. 2015;20:9767–9787. doi: 10.3390/molecules20069767. PubMed DOI PMC

Kos J., Nevin E., Soral M., Kushkevych I., Gonec T., Bobal P., Kollar P., Coffey A., O’Mahony J., Liptaj T., et al. Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene-2-carboxanilides. Bioorg. Med. Chem. 2015;23:2035–2043. doi: 10.1016/j.bmc.2015.03.018. PubMed DOI

Bak A., Kos J., Michnova H., Gonec T., Pospisilova S., Kozik V., Cizek A., Smolinski A., Jampilek J. Consensus-based pharmacophore mapping for new set of N-(disubstituted-phenyl)-3-hydroxyl-naphthalene-2-carboxamides. Int. J. Mol. Sci. 2020;21:6583. doi: 10.3390/ijms21186583. PubMed DOI PMC

Vinsova J., Cermakova K., Tomeckova A., Ceckova M., Jampilek J., Cermak P., Kunes J., Dolezal M., Staud F. Synthesis and antimicrobial evaluation of new 2-substituted 5,7-di-tert-butylbenzoxazoles. Bioorg. Med. Chem. 2006;14:5850–5865. doi: 10.1016/j.bmc.2006.05.030. PubMed DOI

Fajkusova D., Pesko M., Keltosova S., Guo J., Oktabec Z., Vejsova M., Kollar P., Coffey A., Csollei J., Kralova K., et al. Anti-Infective and Herbicidal Activity of N-Substituted 2-Aminobenzothiazoles. Bioorg. Med. Chem. 2012;20:7059–7068. doi: 10.1016/j.bmc.2012.10.007. PubMed DOI

Musiol R., Jampilek J., Nycz J.E., Pesko M., Carroll J., Kralova K., Vejsova M., O’Mahony J., Coffey A., Mrozek A., et al. Investigating the activity spectrum for ring-substituted 8-hydroxyquinolines. Molecules. 2010;15:288–304. doi: 10.3390/molecules15010288. PubMed DOI PMC

Kos J., Zadrazilova I., Nevin E., Soral M., Gonec T., Kollar P., Oravec M., Coffey A., O’Mahony J., Liptaj T., et al. Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents. Bioorg. Med. Chem. 2015;23:4188–4196. doi: 10.1016/j.bmc.2015.06.047. PubMed DOI

Kushkevych I., Vitezova M., Kos J., Kollar P., Jampilek J. Effect of selected 8-hydroxyquinoline-2-carboxanilides on viability and sulfate metabolism of Desulfovibrio piger. J. Appl. Biomed. 2018;16:241–246. doi: 10.1016/j.jab.2018.01.004. DOI

Pospisilova S., Kos J., Michnova H., Kapustikova I., Strharsky T., Oravec M., Moricz A.M., Bakonyi J., Kauerova T., Kollar P., et al. Synthesis and spectrum of biological activities of novel N-arylcinnamamides. Int. J. Mol. Sci. 2018;19:2318. doi: 10.3390/ijms19082318. PubMed DOI PMC

Kos J., Bak A., Kozik V., Jankech T., Strharsky T., Swietlicka A., Michnova H., Hosek J., Smolinski A., Oravec M., et al. Biological activities and ADMET-related properties of novel set of cinnamanilides. Molecules. 2020;25:4121. doi: 10.3390/molecules25184121. PubMed DOI PMC

Strharsky T., Pindjakova D., Kos J., Vrablova L., Michnova H., Hosek J., Strakova N., Lelakova V., Leva L., Kavanova L., et al. Study of biological activities and ADMET-related properties of novel chlorinated N-arylcinnamamides. Int. J. Mol. Sci. 2022;23:3159. doi: 10.3390/ijms23063159. PubMed DOI PMC

Allgauer D.S., Jangra H., Asahara H., Li Z., Chen Q., Zipse H., Ofial A.R., Mayr H. Quantification and theoretical analysis of the electrophilicities of michael acceptors. J. Am. Chem. Soc. 2017;139:13318–13329. doi: 10.1021/jacs.7b05106. PubMed DOI

Liang S.T., Chen C., Chen R.X., Li R., Chen W.L., Jiang G.H., Du L.L. Michael acceptor molecules in natural products and their mechanism of action. Front. Pharmacol. 2022;13:1033003. doi: 10.3389/fphar.2022.1033003. PubMed DOI PMC

Chollet A., Maveyraud L., Lherbet C., Bernardes-Genisson V. An overview on crystal structures of InhA protein: Apo-form, in complex with its natural ligands and inhibitors. Eur. J. Med. Chem. 2018;146:318–343. doi: 10.1016/j.ejmech.2018.01.047. PubMed DOI

Pan P., Knudson S.E., Bommineni G.R., Li H.J., Lai C.T., Liu N., Garcia-Diaz M., Simmerling C., Patil S.S., Slayden R.A., et al. Time-dependent diaryl ether inhibitors of InhA: Structure–activity relationship studies of enzyme inhibition, antibacterial activity, and in vivo efficacy. ChemMedChem. 2014;9:776–791. doi: 10.1002/cmdc.201300429. PubMed DOI PMC

Li H.J., Lai C.T., Pan P., Yu W., Liu N., Bommineni G.R., Garcia-Diaz M., Simmerling C., Tonge P.J. A structural and energetic model for the slow-onset inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA. ACS Chem. Biol. 2014;9:986–993. doi: 10.1021/cb400896g. PubMed DOI PMC

Pliska V., Testa B., van der Waterbeemd H. Lipophilicity in Drug Action and Toxicology. Wiley-VCH; Weinheim, Germany: 1996.

Kerns E.H., Di L. Drug-Like Properties: Concepts. Structure Design and Methods: From ADME to Toxicity Optimization. Academic Press; San Diego, CA, USA: 2008.

Zadrazilova I., Pospisilova S., Pauk K., Imramovsky A., Vinsova J., Cizek A., Jampilek J. In vitro bactericidal activity of 4- and 5-chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA. BioMed Res. Int. 2015;2015:349534. doi: 10.1155/2015/349534. PubMed DOI PMC

Oravcova V., Zurek L., Townsend A., Clark A.B., Ellis J.C., Cizek A. American crows as carriers of vancomycin-resistant enterococci with vanA gene. Environ. Microbiol. 2014;16:939–949. doi: 10.1111/1462-2920.12213. PubMed DOI

Sundarsingh J.A.T., Ranjitha J., Rajan A., Shankar V. Features of the biochemistry of Mycobacterium smegmatis, as a possible model for Mycobacterium tuberculosis. J. Inf. Public. Health. 2020;13:1255–1264. PubMed

Luukinen H., Hammaren M.M., Vanha-Aho L.M., Parikka M. Modeling tuberculosis in Mycobacterium marinum infected adult Zebrafish. J. Vis. Exp. 2018;140:58299. doi: 10.3791/58299. PubMed DOI PMC

Pankey G.A., Sabath L.D. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections. Clin. Infect. Dis. 2004;38:864–870. doi: 10.1086/381972. PubMed DOI

Nubel U., Dordel J., Kurt K., Strommenger B., Westh H., Shukla S.K., Zemlickova H., Leblois R., Wirth T., Jombart T., et al. A timescale for evolution, population expansion, and spatial spread of an emerging clone of methicillin-resistant Staphylococcus aureus. PLoS Pathog. 2010;6:e1000855. doi: 10.1371/journal.ppat.1000855. PubMed DOI PMC

Portela C.A., Smart K.F., Tumanov S., Cook G.M., Villas-Boas S.G. Global metabolic response of Enterococcus faecalis to oxygen. J. Bacteriol. 2014;196:2012–2022. doi: 10.1128/JB.01354-13. PubMed DOI PMC

Gilmore M.S., Clewell D.B., Ike Y., Shankar N. Enterococci: From Commensals to Leading Causes of Drug Resistant Infection. Massachusetts Eye and Ear Infirmary; Boston, MA, USA: 2014. [(accessed on 15 September 2022)]. Available online: https://www.ncbi.nlm.nih.gov/books/NBK190432/ PubMed

Ramos S., Silva V., Dapkevicius M.d.L.E., Igrejas G., Poeta P. Enterococci, from harmless bacteria to a pathogen. Microorganisms. 2020;8:1118. doi: 10.3390/microorganisms8081118. PubMed DOI PMC

Gilmore M.S., Salamzade R., Selleck E., Bryan N., Mello S.S., Manson A.L., Earl A.M. Genes contributing to the unique biology and intrinsic antibiotic resistance of Enterococcus faecalis. mBio. 2020;11:e02962-20. doi: 10.1128/mBio.02962-20. PubMed DOI PMC

Measuring Cell Viability/Cytotoxicity. Dojindo EU GmbH, Munich, Germany. [(accessed on 15 September 2022)]. Available online: https://www.dojindo.eu.com/Protocol/Dojindo-Cell-Proliferation-Protocol.pdf.

Grela E., Kozłowska J., Grabowiecka A. Current methodology of MTT assay in bacteria—A review. Acta Histochem. 2018;120:303–311. doi: 10.1016/j.acthis.2018.03.007. PubMed DOI

Imramovsky A., Pesko M., Kralova K., Vejsova M., Stolarikova J., Vinsova J., Jampilek J. Investigating spectrum of biological activity of 4- and 5-chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benzamides. Molecules. 2011;16:2414–2430. doi: 10.3390/molecules16032414. PubMed DOI PMC

Pauk K., Zadrazilova I., Imramovsky A., Vinsova J., Pokorna M., Masarikova M., Cizek A., Jampilek J. New derivatives of salicylamides: Preparation and antimicrobial activity against various bacterial species. Bioorg. Med. Chem. 2013;21:6574–6581. doi: 10.1016/j.bmc.2013.08.029. PubMed DOI

Pindjakova D., Pilarova E., Pauk K., Michnova H., Hosek J., Magar P., Cizek A., Imramovsky A., Jampilek J. Study of biological activities and ADMET-related properties of salicylanilide-based peptidomimetics. Int. J. Mol. Sci. 2022;23:11648. doi: 10.3390/ijms231911648. PubMed DOI PMC

Pospisilova S., Kos J., Michnova H., Strharsky T., Cizek A., Jampilek J. N-Arylcinnamamides as antistaphylococcal agents; Proceedings of the 4th International Electronic Conference on Medicinal Chemistry, ECMC-4; 1–30 November 2018; [(accessed on 16 November 2022)]. p. 5576. Available online: https://sciforum.net/manuscripts/5576/slides.pdf.

Sundaramoorthy N.S., Mitra K., Ganesh J.S., Makala H., Lotha R., Bhanuvalli S.R., Ulaganathan V., Tiru V., Sivasubramanian A., Nagarajan S. Ferulic acid derivative inhibits NorA efflux and in combination with ciprofloxacin curtails growth of MRSA in vitro and in vivo. Microb. Pathog. 2018;124:54–62. doi: 10.1016/j.micpath.2018.08.022. PubMed DOI

Pinheiro P.G., Santiago G.M.P., da Silva F.E.F., de Araujo A.C.J., de Oliveira C.R.T., Freitas P.R., Rocha J.E., de Araujo Neto J.B., Costa da Silva M.M., Tintino S.R., et al. Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives. Asian Pac. J. Trop. Biomed. 2021;11:405–413.

Hemaiswarya S., Doble M. Synergistic interaction of phenylpropanoids with antibiotics against bacteria. J. Med. Microbiol. 2010;59:1469–1476. doi: 10.1099/jmm.0.022426-0. PubMed DOI

Sun L., Rogiers G., Michiels C.W. The natural antimicrobial trans-cinnamaldehyde interferes with UDP-N-acetylglucosamine biosynthesis and cell wall homeostasis in Listeria monocytogenes. Foods. 2021;10:1666. doi: 10.3390/foods10071666. PubMed DOI PMC

Jampilek J., Kos J., Strharsky T., Pindjakova D., Vrablova L., Jankech T., Gonec T., Cizek A. Investigation of novel halogenated cinnamanilides; Proceedings of the 11th International Conference on Biomedical Engineering and Biotechnology, ICBEB 2022; Shenzhen, China. 15–18 November 2022; p. 18.

Gill A.O., Holley R.A. Inhibition of membrane bound ATPases of Escherichia coli and Listeria monocytogenes by plant oil aromatics. Int. J. Food Microbiol. 2006;3:170–174. doi: 10.1016/j.ijfoodmicro.2006.04.046. PubMed DOI

Kos J., Degotte G., Pindjakova D., Strharsky T., Jankech T., Gonec T., Francotte P., Frederich M., Jampilek J. Insights into antimalarial activity of N-phenyl-substituted cinnamanilides. Molecules. 2022;27:7799. doi: 10.3390/molecules27227799. PubMed DOI PMC

Hosek J., Kos J., Strharsky T., Cerna L., Starha P., Vanco J., Travnicek Z., Devinsky F., Jampilek J. Investigation of anti-inflammatory potential of N-arylcinnamamide derivatives. Molecules. 2019;24:4531. doi: 10.3390/molecules24244531. PubMed DOI PMC

Mayer R.J., Ofial A.R. Nucleophilicity of glutathione: A link to Michael acceptor reactivities. Angew. Chem. Int. Ed. Engl. 2019;58:17704–17708. doi: 10.1002/anie.201909803. PubMed DOI PMC

Hearn B.R., Fontaine S.D., Schneider E.L., Kraemer Y., Ashley G.W., Santi D.V. Attenuation of the reaction of Michael acceptors with biologically important nucleophiles. Bioconjug. Chem. 2021;32:794–800. doi: 10.1021/acs.bioconjchem.1c00075. PubMed DOI

Dinkova-Kostova A.T., Massiah M.A., Bozak R.E., Hicks R.J., Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc. Natl. Acad. Sci. USA. 2001;98:3404–3409. doi: 10.1073/pnas.051632198. PubMed DOI PMC

Previti S., Ettari R., Di Chio C., Ravichandran R., Bogacz M., Hellmich U.A., Schirmeister T., Cosconati S., Zappala M. Development of reduced peptide bond pseudopeptide Michael acceptors for the treatment of human african Trypanosomiasis. Molecules. 2022;27:3765. doi: 10.3390/molecules27123765. PubMed DOI PMC

Chu H.W., Sethy B., Hsieh P.W., Horng J.T. Identification of potential drug targets of broad-spectrum inhibitors with a Michael acceptor moiety using shotgun proteomics. Viruses. 2021;13:1756. doi: 10.3390/v13091756. PubMed DOI PMC

Jackson P.A., Widen J.C., Harki D.A., Brummond K.M. Covalent modifiers: A chemical perspective on the reactivity of α,β-unsaturated carbonyls with thiols via hetero-Michael addition reactions. J. Med. Chem. 2017;60:839–885. doi: 10.1021/acs.jmedchem.6b00788. PubMed DOI PMC

Steenackers W., El Houari I., Baekelandt A., Witvrouw K., Dhondt S., Leroux O., Gonzalez N., Corneillie S., Cesarino I., Inze D., et al. cis-Cinnamic acid is a natural plant growth-promoting compound. J. Exp. Bot. 2019;70:6293–6304. doi: 10.1093/jxb/erz392. PubMed DOI PMC

Yen G.C., Chen Y.L., Sun F.M., Chiang Y.L., Lu S.H., Weng C.J. A comparative study on the effectiveness of cis- and trans-form of cinnamic acid treatments for inhibiting invasive activity of human lung adenocarcinoma cells. Eur. J. Pharm. Sci. 2011;44:281–287. doi: 10.1016/j.ejps.2011.08.006. PubMed DOI

Chen Y.L., Huang S.T., Sun F.M., Chiang Y.L., Chiang C.J., Tsai C.M., Weng C.J. Transformation of cinnamic acid from trans- to cis-form raises a notable bactericidal and synergistic activity against multiple-drug resistant Mycobacterium tuberculosis. Eur. J. Pharm. Sci. 2011;43:188–194. doi: 10.1016/j.ejps.2011.04.012. PubMed DOI

Zhang Y., Wei J., Qiu Y., Niu C., Song Z., Yuan Y., Yue T. Structure-dependent inhibition of Stenotrophomonas maltophilia by polyphenol and its impact on cell membrane. Front. Microbiol. 2019;10:2646. doi: 10.3389/fmicb.2019.02646. PubMed DOI PMC

Sullivan T.J., Truglio J.J., Boyne M.E., Novichenok P., Zhang X., Stratton C.F., Li H.J., Kaur T., Amin A., Johnson F., et al. High affinity InhA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis. ACS Chem. Biol. 2006;1:43–53. doi: 10.1021/cb0500042. PubMed DOI

Koul A., Dendouga N., Vergauwen K., Molenberghs B., Vranckx L., Willebrords R., Ristic Z., Lill H., Dorange I., Guillemont J., et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat. Chem. Biol. 2007;3:323–324. doi: 10.1038/nchembio884. PubMed DOI

Balemans W., Vranckx L., Lounis N., Pop O., Guillemont J., Vergauwen K., Mol S., Gilissen R., Motte M., Lancois D., et al. Novel antibiotics targeting respiratory atp synthesis in Gram-positive pathogenic bacteria. Antimicrob. Agents Chemother. 2012;56:4131–4139. doi: 10.1128/AAC.00273-12. PubMed DOI PMC

Qiu J., Zhang R. DDQ-Promoted direct transformation of benzyl hydrocarbons to amides via tandem reaction of the CDC reaction and Beckmann rearrangement. Org. Biomol. Chem. 2013;45:6008–6012. doi: 10.1039/c3ob41218k. PubMed DOI

Choi J.W., Jang B.K., Cho N., Park J.H., Yeon S.K., Ju E.J., Lee Y.S., Han G., Pae A.N., Kim D.J., et al. Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors. Bioorg. Med. Chem. 2015;23:6486–6496. doi: 10.1016/j.bmc.2015.08.012. PubMed DOI

Qin C., Zhou W., Chen F., Ou Y., Jiao N. Iron-catalyzed C-H and C-C bond cleavage: A direct approach to amides from simple hydrocarbons. Angew. Chem. Int. Ed. Engl. 2011;50:12595–12599. doi: 10.1002/anie.201106112. PubMed DOI

Pandia B.K., Gunanathan C. Manganese(I) catalyzed α-alkenylation of amides using alcohols with liberation of hydrogen and water. J. Org. Chem. 2021;86:9994–10005. doi: 10.1021/acs.joc.1c00685. PubMed DOI

National Committee for Clinical Laboratory Standards . Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 11th ed. NCCLS; Wayne, PA, USA: 2018. M07.

Schwalbe R., Steele-Moore L., Goodwin A.C. Antimicrobial Susceptibility Testing Protocols. CRC Press; Boca Raton, FL, USA: 2007.

Scandorieiro S., de Camargo L.C., Lancheros C.A., Yamada-Ogatta S.F., Nakamura C.V., de Oliveira A.G., Andrade C.G., Duran N., Nakazato G., Kobayashi R.K. Synergistic and additive effect of oregano essential oil and biological silver nanoparticles against multidrug-resistant bacterial strains. Front. Microbiol. 2016;7:760. doi: 10.3389/fmicb.2016.00760. PubMed DOI PMC

Guimaraes A.C., Meireles L.M., Lemos M.F., Guimaraes M.C.C., Endringer D.C., Fronza M., Scherer R. Antibacterial activity of terpenes and terpenoids present in essential oils. Molecules. 2019;24:2471. doi: 10.3390/molecules24132471. PubMed DOI PMC

Kos J., Kozik V., Pindjakova D., Jankech T., Smolinski A., Stepankova S., Hosek J., Oravec M., Jampilek J., Bak A. Synthesis and hybrid SAR property modeling of novel cholinesterase inhibitors. Int. J. Mol. Sci. 2021;22:3444. doi: 10.3390/ijms22073444. PubMed DOI PMC

Schrodinger . The PyMOL Molecular Graphics System. Schrodinger, LLC; New York, NY, USA: 2021. Version 2.5.

Case D.A., Aktulga H.M., Belfon K., Ben-Shalom I.Y., Berryman J.T., Brozell S.R., Cerutti D.S., Cheatham T.E., Cisneros G.A., Cruzeiro V.W.D., et al. Amber 2022, University of California: San Francisco, CA, USA. 2022. [(accessed on 20 October 2022)]. Available online: https://ambermd.org/index.php.

Liu T., Lin Y., Wen X., Jorissen R.N., Gilson M.K. BindingDB: A web-accessible database of experimentally determined protein–ligand binding affinities. Nucleic Acids Res. 2007;35:198–201. doi: 10.1093/nar/gkl999. PubMed DOI PMC

O’Boyle N.M., Banck M., James C.A., Morley C., Vandermeersch T., Hutchison G.R. Open babel: An open chemical toolbox. J. Cheminform. 2011;3:33. doi: 10.1186/1758-2946-3-33. PubMed DOI PMC

Trott O., Olson A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2010;31:455–461. doi: 10.1002/jcc.21334. PubMed DOI PMC

Eberhardt J., Santos-Martins D., Tillack A.F., Forli S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model. 2021;61:3891–3898. doi: 10.1021/acs.jcim.1c00203. PubMed DOI PMC

Critical view on antimicrobial, antibiofilm and cytotoxic activities of quinazolin-4(3H)-one derived schiff bases and their Cu(II) complexes